Results of mutation analysis of WASP gene
Patient . | Genomic DNA mutation . | Exon or intron . | cDNA mutation (predicted protein change) . | Score . | Western blot . | |
|---|---|---|---|---|---|---|
| Missense mutation: 13 families, 16 patients | ||||||
| 1*, 2* | 52G > A | Exon 1 | 52G > A (Met6Ile) | 1, 1 | Positive | |
| 3 | 105C > T | Exon 1 | 105C > T (Ser24Phe) | 5A | Positive | |
| 4, 5 | 168C > T | Exon 2 | 168C > T (Thr45Met) | 1, 2 | Positive | |
| 6 | 168C > T | Exon 2 | 168C > T (Thr45Met) | 5A | Positive | |
| 7* | 168C > T | Exon 2 | 168C > T (Thr45Met) | 2 | Positive | |
| 8 | 201C > T | Exon 2 | 201C > T (Ala56Val) | 1 | Positive | |
| 9, 10 | 257G > A | Exon 2 | 257G > A (Val75Met) | 2, 1 | Positive | |
| 11 | 290C > T | Exon 2 | 290C > T (Arg86Cys) | 2 | Positive | |
| 12 | 290C > T | Exon 2 | 290C > T (Arg86Cys) | 5A | Positive | |
| 13 | 290C > T | Exon 2 | 290C > T (Arg86Cys) | 1 | Positive | |
| 14 | 291G > A | Exon 2 | 291G > A (Arg86His) | 2 | Positive | |
| 15* | 291G > A | Exon 2 | 291G > A (Arg86His) | 3 | Positive | |
| 16 | 291G > A | Exon 2 | 291G > A (Arg86His) | 5A | Positive | |
| Nonsense mutation: 4 families, 5 patients | ||||||
| 17 | 71C > T | Exon 1 | 71C > T (Arg13Stop) | 3 | Negative | |
| 18* | 131C > T | Exon 1 | 131C > T (Gln33Stop) | 4 | Negative | |
| 19* | 196C > A | Exon 2 | 196C > A (Tyr54Stop) | 3 | Negative | |
| 20, 21 | 995C > T | Exon 10 | 995C > T (Arg321Stop) | 3, 4 | Positive, truncated | |
| Deletion: 7 families, 7 patients | ||||||
| 22* | 41-45delG | Exon 1 | 41-45delG (frameshift, stop aa 44) | 4 | Negative | |
| 23 | 140-142delTT | Exon 1 | 140-142delTT (frameshift, stop aa 36) | 2 | Negative | |
| 24 | 260-261delA | Exon 2 | 260-261delA (frameshift, stop aa 126) | 5A/M | Negative | |
| 25 | 283-287del 5 nt | Exon 2 | 283-287del 5 nt (frameshift, stop aa 119) | 4 | Negative | |
| 26 | 406-409delG | Exon 4 | 406-409delG (frameshift, stop aa 126) | 4 | Negative | |
| 27* | 899delC | Exon 9 | 899delC (frameshift, stop aa 307) | 3 | Negative | |
| 28 | 1178-1182delC | Exon 10 | 1178-1182delC (frameshift, stop aa 444) | 3 | Negative | |
| Large deletion: 3 families, 3 patients | ||||||
| 29* | del 1872 nt (2932-4803 nt§) | Exons 3-7 | del exons 3-7 (308-768) (frameshift, stop aa 105) | 5A | Negative | |
| 30 | del 1558 nt (3991-5548 nt§) | Exon 7 | del exon 7 (594-768) (frameshift, stop aa 202) | 5A/M | Negative | |
| 31 | del total WASP gene | Exons 1-12 | del total WASP gene | 3 | Negative | |
| Insertion: 1 family, 1 patient | ||||||
| 32 | 62-64insC | Exon 1 | 62-64insC (frameshift, stop aa 37) | 5M | Negative | |
| Splice anomaly: 15 families, 18 patients | ||||||
| 33 | T > G, + 2 | Intron 1 | ins intron 1 (297 nt) (stop aa 113) | 3 | Negative | |
| 34 | G > A, -1 | Intron 3 | ins intron 3 (100 nt) (frameshift, stop aa 201) | 5M | Negative | |
| del 28 nt of exon 4 (395-422) (frameshift, stop aa 251) | ||||||
| 35 | G > A, + 1 | Intron 3 | del exon 3 (308-394) (del aa's 92-120)∥ | 3 | Positive, normal size | |
| 36 | del 8 nt, + 1 to + 8 | Intron 4 | ins 31 nt of intron 4 (frameshift, stop aa 178)∥ | 1 | Positive, normal size | |
| del exon 4 (395-497) (frameshift, stop aa 251) | ||||||
| 37 | 539G > T | Exon 5 | del exon 5 (498-539) (del aa's 155-169) | 2 | Positive, small MW | |
| 539G > T (Asn169Stop) | ||||||
| 38,† 39, 40 | G > A, + 5 | Intron 6 | ins 38 nt of intron 6 (frameshift stop aa 190)∥ | 5A, 1, 4 | Positive, normal size | |
| 41‡ | G > A, + 5 | Intron 6 | ins 38 nt of intron 6 (frameshift stop aa 190)∥ | 2 | Positive, normal size | |
| 42* | del G, - 1 | Intron 7 | del exon 8 (769-811) (frameshift, stop aa 246) | 5A | Negative | |
| 43 | G > C, + 1 | Intron 8 | del exon 8 (769-811) (frameshift, stop aa 246) | 5A | Negative | |
| 44 | del 4 nt, + 1 to + 4 | Intron 8 | ND | 4 | Negative | |
| 45 | del 4 nt, + 1 to + 4 | Intron 8 | ND | 5M | Negative | |
| 46 | del 4 nt, + 1 to + 4 | Intron 8 | del exon 8 (769-811) (frameshift, stop aa 246) | 4 | Negative | |
| del exon 8, 9 (769-830) (frameshift, stop aa 267) | ||||||
| ins intron 9 (frameshift, stop aa 327) | ||||||
| 47 | No mutation in coding region | — | ins intron 9 (frameshift, stop aa 327)∥ | 1 | Positive, normal size | |
| del exon 10 (966-1372) (frameshift, stop aa 357) | ||||||
| 48 | No mutation in coding region | — | ins intron 11 (118 bp) (frameshift, stop aa 520)∥ | 3 | Positive, normal size | |
| 49, 50 | No mutation in coding region | — | ins intron 11 (118 bp) (frameshift, stop aa 520)∥ | 5A, 5A | Positive, normal size | |
Patient . | Genomic DNA mutation . | Exon or intron . | cDNA mutation (predicted protein change) . | Score . | Western blot . | |
|---|---|---|---|---|---|---|
| Missense mutation: 13 families, 16 patients | ||||||
| 1*, 2* | 52G > A | Exon 1 | 52G > A (Met6Ile) | 1, 1 | Positive | |
| 3 | 105C > T | Exon 1 | 105C > T (Ser24Phe) | 5A | Positive | |
| 4, 5 | 168C > T | Exon 2 | 168C > T (Thr45Met) | 1, 2 | Positive | |
| 6 | 168C > T | Exon 2 | 168C > T (Thr45Met) | 5A | Positive | |
| 7* | 168C > T | Exon 2 | 168C > T (Thr45Met) | 2 | Positive | |
| 8 | 201C > T | Exon 2 | 201C > T (Ala56Val) | 1 | Positive | |
| 9, 10 | 257G > A | Exon 2 | 257G > A (Val75Met) | 2, 1 | Positive | |
| 11 | 290C > T | Exon 2 | 290C > T (Arg86Cys) | 2 | Positive | |
| 12 | 290C > T | Exon 2 | 290C > T (Arg86Cys) | 5A | Positive | |
| 13 | 290C > T | Exon 2 | 290C > T (Arg86Cys) | 1 | Positive | |
| 14 | 291G > A | Exon 2 | 291G > A (Arg86His) | 2 | Positive | |
| 15* | 291G > A | Exon 2 | 291G > A (Arg86His) | 3 | Positive | |
| 16 | 291G > A | Exon 2 | 291G > A (Arg86His) | 5A | Positive | |
| Nonsense mutation: 4 families, 5 patients | ||||||
| 17 | 71C > T | Exon 1 | 71C > T (Arg13Stop) | 3 | Negative | |
| 18* | 131C > T | Exon 1 | 131C > T (Gln33Stop) | 4 | Negative | |
| 19* | 196C > A | Exon 2 | 196C > A (Tyr54Stop) | 3 | Negative | |
| 20, 21 | 995C > T | Exon 10 | 995C > T (Arg321Stop) | 3, 4 | Positive, truncated | |
| Deletion: 7 families, 7 patients | ||||||
| 22* | 41-45delG | Exon 1 | 41-45delG (frameshift, stop aa 44) | 4 | Negative | |
| 23 | 140-142delTT | Exon 1 | 140-142delTT (frameshift, stop aa 36) | 2 | Negative | |
| 24 | 260-261delA | Exon 2 | 260-261delA (frameshift, stop aa 126) | 5A/M | Negative | |
| 25 | 283-287del 5 nt | Exon 2 | 283-287del 5 nt (frameshift, stop aa 119) | 4 | Negative | |
| 26 | 406-409delG | Exon 4 | 406-409delG (frameshift, stop aa 126) | 4 | Negative | |
| 27* | 899delC | Exon 9 | 899delC (frameshift, stop aa 307) | 3 | Negative | |
| 28 | 1178-1182delC | Exon 10 | 1178-1182delC (frameshift, stop aa 444) | 3 | Negative | |
| Large deletion: 3 families, 3 patients | ||||||
| 29* | del 1872 nt (2932-4803 nt§) | Exons 3-7 | del exons 3-7 (308-768) (frameshift, stop aa 105) | 5A | Negative | |
| 30 | del 1558 nt (3991-5548 nt§) | Exon 7 | del exon 7 (594-768) (frameshift, stop aa 202) | 5A/M | Negative | |
| 31 | del total WASP gene | Exons 1-12 | del total WASP gene | 3 | Negative | |
| Insertion: 1 family, 1 patient | ||||||
| 32 | 62-64insC | Exon 1 | 62-64insC (frameshift, stop aa 37) | 5M | Negative | |
| Splice anomaly: 15 families, 18 patients | ||||||
| 33 | T > G, + 2 | Intron 1 | ins intron 1 (297 nt) (stop aa 113) | 3 | Negative | |
| 34 | G > A, -1 | Intron 3 | ins intron 3 (100 nt) (frameshift, stop aa 201) | 5M | Negative | |
| del 28 nt of exon 4 (395-422) (frameshift, stop aa 251) | ||||||
| 35 | G > A, + 1 | Intron 3 | del exon 3 (308-394) (del aa's 92-120)∥ | 3 | Positive, normal size | |
| 36 | del 8 nt, + 1 to + 8 | Intron 4 | ins 31 nt of intron 4 (frameshift, stop aa 178)∥ | 1 | Positive, normal size | |
| del exon 4 (395-497) (frameshift, stop aa 251) | ||||||
| 37 | 539G > T | Exon 5 | del exon 5 (498-539) (del aa's 155-169) | 2 | Positive, small MW | |
| 539G > T (Asn169Stop) | ||||||
| 38,† 39, 40 | G > A, + 5 | Intron 6 | ins 38 nt of intron 6 (frameshift stop aa 190)∥ | 5A, 1, 4 | Positive, normal size | |
| 41‡ | G > A, + 5 | Intron 6 | ins 38 nt of intron 6 (frameshift stop aa 190)∥ | 2 | Positive, normal size | |
| 42* | del G, - 1 | Intron 7 | del exon 8 (769-811) (frameshift, stop aa 246) | 5A | Negative | |
| 43 | G > C, + 1 | Intron 8 | del exon 8 (769-811) (frameshift, stop aa 246) | 5A | Negative | |
| 44 | del 4 nt, + 1 to + 4 | Intron 8 | ND | 4 | Negative | |
| 45 | del 4 nt, + 1 to + 4 | Intron 8 | ND | 5M | Negative | |
| 46 | del 4 nt, + 1 to + 4 | Intron 8 | del exon 8 (769-811) (frameshift, stop aa 246) | 4 | Negative | |
| del exon 8, 9 (769-830) (frameshift, stop aa 267) | ||||||
| ins intron 9 (frameshift, stop aa 327) | ||||||
| 47 | No mutation in coding region | — | ins intron 9 (frameshift, stop aa 327)∥ | 1 | Positive, normal size | |
| del exon 10 (966-1372) (frameshift, stop aa 357) | ||||||
| 48 | No mutation in coding region | — | ins intron 11 (118 bp) (frameshift, stop aa 520)∥ | 3 | Positive, normal size | |
| 49, 50 | No mutation in coding region | — | ins intron 11 (118 bp) (frameshift, stop aa 520)∥ | 5A, 5A | Positive, normal size | |
Patients 1 and 2 are brothers; patients 4 and 5 are cousins; patient 10 is a grandfather of patient 9; patients 20 and 21 are brothers; patient 38 is a cousin of patients 39 and 40, who are brothers; patients 49 and 50 are brothers. Score 5A or 5M is score 5 with autoimmune disease (A) or malignancy (M), respectively. ND indicates not done; —, not applicable; and MW, molecular weight.
Reported by Itoh et al.12
Reported by Kawakami et al.13
Reported by Inoue et al.14
Nucleotide numbers are from GenBank accession no. AF115549.16
Normally spliced cDNA of the WASP gene was also detected with abnormally spliced cDNA.